Gastroparesis is a disorder of gastric function characterized by delay in gastric emptying, frequently associated with chronic nausea and vomiting, early satiety, postprandial fullness, abdominal pain, and malnutrition that may require nutritional support. The broad objectives of this proposal is to improve our understanding of this disorder and advancing the diagnosis and treatment of gastroparesis and related disorders. We propose to do this through three specific aims, as follows: Specific Aim 1: To complete ongoing and approved studies initiated by the NIH-funded GpCRC (the Gastroparesis Clinical Research Consortium, a collaboration between six clinical sites and data coordinating center). These include (1) a randomized trial of nortriptyline vs. placebo for idiopathic gastroparesis, (2) a pilot study of safety, feasibility and potential efficacy of continuous glucose monitoring and insulin pump therapy in diabetic gastroparesis, (3) a randomized trial of aprepitant vs. placebo for the relief of nausea in patients with chronic nausea and vomiting of presumed gastric origin and (4) a tissue study from full thickness gastric biopsies. Specific Aim 2: To maintain, expand, and refine the Gastroparesis Registry (ClinicalTrials.gov NCT00398801) in order to enable critical additional analyses of the clinical data and biosamples. The first Registry patient with gastroparesis was recruited in February 2007 and a total of 587 patients were enrolled by end of recruitment in March 2010. Our aim is to have at least four years of follow-up on all patients and with up to 9 years for some patients. This will require maintenance of the Registry and continued periodic follow-up visits over the next five years. Specific Aim 3: To understand nitrergic control of gastric sensorimotor function: correlation with gender, diabetes and gastric emptying phenotype in patients with gastroparesis and chronic unexplained nausea and vomiting.